We will investigate the coronary arterial vasculature to determine the role of vascular remodeling in coronary vascular pathology. Inward remodeling results in a reduction of maximum vessel lumen diameter and compromises coronary blood flow. Vascular remodeling has been implicated in coronary flow complications associated with atherosclerosis, hypertension, restenosis and the pathologies of coronary bypass surgery. Our hypothesis is that vascular tone is the primary trigger for coronary arterial inward remodeling. Because many circulating factors found in vivo affect vascular tone, and because in vivo vascular hemodynamics are inherently complex, a novel in vitro system will be used that can simplify and separately examine contributing factors. Cannulated, perfused vessel segments cultured in the system maintain intact smooth muscle function and endothelium dependent dilation for up to fourteen days. Among other broader experimental objectives, the specific objective of this study to be undertaken during the course of my sabbatical is to determine the effect of conditions common to coronary artery disease on in vitro coronary vascular remodeling. Additionally, by conducting initial studies on ovarian resistance arteries, I also will undertake these objectives: to determine whether cyclic remodeling of ovarian resistance vessels occurs in vivo; and to optimize techniques for the culturing of ovarian resistance vessels.